IL-12 receptor (IL-12R) expression and accumulation of IL-12R beta 1 and IL-12R beta 2 mRNAs in CD4+ T cells by costimulation with B7-2 molecules.
IL-12 is a crucial cytokine for the determination of a Th1/Th2 balance. It is important, therefore, to elucidate the mechanisms of IL-12R expression on Th cells. In this report, we present evidence to show that B7-2 costimulation plays a pivotal role in the expression of IL-12R on Th cells. A Th1 clone expressed a low density of IL-12R in a resting condition, the expression was enhanced by stimulation with specific Ag on splenic adherent cells and the enhancement was inhibited by anti-B7-2 or CTLA-4-Ig. When stimulated with anti-CD3 plus B7-2-transfected Chinese hamster ovary (CHO) cells, the clone strongly expressed IL-12R, although anti-CD3 by itself only weakly enhanced the expression. We obtained results that were similar to those in the Th1 clone in CD4+ CD45RB(low) memory T cells. In CD4+ CD44(low) naive T cells, costimulation with B7-2-CHO was found to play a more important role in IL-12R expression. The accumulation of both IL-12R beta 1 and -beta 2 chain mRNAs was detected in naive T cells only when they were costimulated with anti-CD3 and B7-2-CHO, but beta 2 mRNA was not expressed upon anti-CD3 stimulation alone. On the other hand, both Th1 clones and memory T cells expressed low amounts of these mRNA without any stimulation, and the expression was weakly enhanced by anti-CD3 stimulation alone. For the maximum expression of these mRNAs, however, these cells also required costimulation with anti-CD3 and B7-2-CHO.
Igarashi
O
O
Department of Allergology, Institute of Medical Science, University of Tokyo, Japan.
Yamane
H
H
Imajoh-Ohmi
S
S
Nariuchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D002999:Clone Cells; D006224:Cricetinae; D005260:Female; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000378:metabolism*; D007399:Interphase / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053707:Receptors, Interleukin-12; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D017252:CD3 Complex; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12